Nevin Manimala

Ann Surg Oncol. 2023 Nov 11. doi: 10.1245/s10434-023-14240-6. Online ahead of print.

ABSTRACT

BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin.

PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m². The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity.

RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death.

CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.

PMID:37952018 | DOI:10.1245/s10434-023-14240-6

Biol Trace Elem Res. 2023 Nov 11. doi: 10.1007/s12011-023-03942-3. Online ahead of print.

ABSTRACT

Concentrations of metal(loid)s, Ag, Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Se, Sr, V and Zn, were determined in rice on sale in Las Vegas. The rice samples were grown in five different countries, the USA, Thailand, India, Pakistan, and Bangladesh. The elemental concentrations in rice grain were determined using inductively coupled plasma mass spectrometry (ICP-MS) following hot block-assisted digestion. The accuracy of the laboratory procedure was verified by the analysis of rice flour standard reference material (NIST SRM 1568b). The mean metal(loid) contents in rice of various geographic origins were 3.18-5.91 mg kg^-1 for Al, 0.05-0.12 mg kg^-1 for As, 3.64-41 μg kg^-1 for Cd, 5.11-12 μg kg^-1 for Co, 0.12-0.14 mg kg^-1 for Cr, 1.5-1.91 mg kg^-1 for Cu, 3.04-4.98 mg kg^-1 for Fe, 4.2-10.4 mg kg^-1 for Mn, 0.21-0.41 mg kg^-1 for Ni, 0.02-0.07 mg kg^-1 for Se, 0.68-0.88 mg kg^-1 for Sr, 3.64-5.26 μg kg^-1 for V, and 16.6-19.9 mg kg^-1 for Zn. respectively. The mean concentration of As in US rice was significantly higher than in Indian, Pakistani, and Bangladeshi rice. On the other hand, it was found a significantly low mean level of Cd in US-grown rice. It was also found that the concentrations of metal(loid)s in black and brown rice on sale in Las Vegas were statistically similar, except for Mn and Se. The geographic origin traceability of rice grain involved the use of ICP-MS analysis coupled with chemometrics that allowed their differentiation based on the rice metal(loid) profile, thus confirming their origins. Data were processed by linear discriminant analysis, and US and Thai rice samples were cross-validated with higher accuracy (100%). This authentication quickly discriminates US rice from the other regions and adds verifiable food safety measures for consumers.

PMID:37952013 | DOI:10.1007/s12011-023-03942-3

Sci Rep. 2023 Nov 11;13(1):19694. doi: 10.1038/s41598-023-46812-7.

ABSTRACT

Diffusion and mobility are essential for cellular functions, as molecules are usually distributed throughout the cell and have to meet to interact and perform their function. This also involves the cytosolic migration of cellular organelles. However, observing such diffusion and interaction dynamics is challenging due to the high spatial and temporal resolution required and the accurate analysis of the diffusional tracks. The latter is especially important when identifying anomalous diffusion events, such as directed motions, which are often rare. Here, we investigate the migration modes of peroxisome organelles in the cytosol of living cells. Peroxisomes predominantly migrate randomly, but occasionally they bind to the cell’s microtubular network and perform directed migration, which is difficult to quantify, and so far, accurate analysis of switching between these migration modes is missing. We set out to solve this limitation by experiments and analysis with high statistical accuracy. Specifically, we collect temporal diffusion tracks of thousands of individual peroxisomes in the HEK 293 cell line using two-dimensional spinning disc fluorescence microscopy at a high acquisition rate of 10 frames/s. We use a Hidden Markov Model with two hidden states to (1) automatically identify directed migration segments of the tracks and (2) quantify the migration properties for comparison between states and between different experimental conditions. Comparing different cellular conditions, we show that the knockout of the peroxisomal membrane protein PEX14 leads to a decrease in the directed movement due to a lowered binding probability to the microtubule. However, it does not eradicate binding, highlighting further microtubule-binding mechanisms of peroxisomes than via PEX14. In contrast, structural changes of the microtubular network explain perceived eradication of directed movement by disassembly of microtubules by Nocodazole-treatment.

PMID:37951993 | DOI:10.1038/s41598-023-46812-7

Eye (Lond). 2023 Nov 11. doi: 10.1038/s41433-023-02817-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine event-based glaucoma progression using optical coherence tomography (OCT) and OCT angiography (OCTA).

METHODS: In this retrospective study, glaucoma eyes with ≥2-year and 4-visits of OCT/OCTA imaging were included. Peripapillary capillary density (CD) and retinal nerve fibre layer thickness (RNFL) were obtained from 4.5 mm × 4.5 mm optic nerve head (ONH) scans. Event-based OCT/OCTA progression was defined as decreases in ONH measurements exceeding test-retest variability on ≥2 consecutive visits. Visual field (VF) progression was defined as significant VF mean deviation worsening rates on ≥2 consecutive visits. Inter-instrument agreement on progression detection was compared using kappa(κ) statistics.

RESULTS: Among 147 eyes (89 participants), OCTA and OCT identified 33(22%) and 25(17%) progressors, respectively. They showed slight agreement (κ = 0.06), with 7(5%) eyes categorized as progressors by both. When incorporating both instruments, the rate of progressors identified increased to 34%. Similar agreement was observed in diagnosis- and severity-stratified analyses (κ < 0.10). Compared to progressors identified only by OCT, progressors identified only by OCTA tended to have thinner baseline RNFL and worse baseline VF. VF progression was identified in 11(7%) eyes. OCT and VF showed fair agreement (κ = 0.26), with 6(4%) eyes categorized as progressors by both. OCTA and VF showed slight agreement (κ = 0.08), with 4(3%) eyes categorized as progressors by both.

CONCLUSIONS: OCT and OCTA showed limited agreement on event-based progression detection, with OCT showing better agreement with VF. Both OCT and OCTA detected more progressors than VF. OCT and OCTA may provide valuable, yet different and complementary, information about glaucoma progression.

PMID:37951976 | DOI:10.1038/s41433-023-02817-0

Br J Cancer. 2023 Nov 11. doi: 10.1038/s41416-023-02492-8. Online ahead of print.

ABSTRACT

BACKGROUND: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant PC (nmCRPC) in the Phase 3 randomised TITAN and SPARTAN studies, respectively, and maintained health-related quality of life (HRQoL). Apalutamide treatment effect by patient age requires assessment.

METHODS: Post-hoc analysis assessed patients receiving 240 mg/day apalutamide (525 TITAN and 806 SPARTAN) or placebo (527 TITAN and 401 SPARTAN) with ongoing ADT, stratified by age groups. Prostate-specific antigen declines, radiographic progression-free survival, metastasis-free survival, overall survival (OS), HRQoL and safety were assessed using descriptive statistics, Kaplan-Meier method, Cox proportional-hazards model and mixed-effects model for repeated measures.

RESULTS: Hazard ratios (95% confidence intervals) generally favoured apalutamide plus ADT versus ADT alone across all endpoints regardless of age; e.g., OS values were 0.57 (0.40-0.80), 0.70 (0.54-0.91) and 0.74 (0.40-1.39) (TITAN) and 0.39 (0.19-0.78), 0.89 (0.69-1.16) and 0.81 (0.58-1.15) (SPARTAN) in patients aged <65, 65-79 and ≥80 years. Regardless of age, apalutamide also maintained HRQoL and was tolerated well with a potential trend in rates of adverse events increasing with age. Limitations include post-hoc nature and variability in sample size of age groups.

CONCLUSIONS: Apalutamide plus ADT was an effective and well-tolerated option maintaining HRQoL in patients with mCSPC and nmCRPC regardless of age.

CLINICAL TRIAL REGISTRATION: TITAN (NCT02489318); SPARTAN (NCT01946204).

PMID:37951974 | DOI:10.1038/s41416-023-02492-8

Nat Commun. 2023 Nov 11;14(1):7311. doi: 10.1038/s41467-023-42868-1.

ABSTRACT

Human social interactions tend to vary in intensity over time, whether they are in person or online. Variable rates of interaction in structured populations can be described by networks with the time-varying activity of links and nodes. One of the key statistics to summarize temporal patterns is the inter-event time, namely the duration between successive pairwise interactions. Empirical studies have found inter-event time distributions that are heavy-tailed, for both physical and digital interactions. But it is difficult to construct theoretical models of time-varying activity on a network that reproduce the burstiness seen in empirical data. Here we develop a spanning-tree method to construct temporal networks and activity patterns with bursty behavior. Our method ensures any desired target inter-event time distributions for individual nodes and links, provided the distributions fulfill a consistency condition, regardless of whether the underlying topology is static or time-varying. We show that this model can reproduce burstiness found in empirical datasets, and so it may serve as a basis for studying dynamic processes in real-world bursty interactions.

PMID:37951967 | DOI:10.1038/s41467-023-42868-1

Lipids Health Dis. 2023 Nov 11;22(1):193. doi: 10.1186/s12944-023-01958-1.

ABSTRACT

BACKGROUND: The association between triglyceride-glucose (TyG) index and poor prognosis remains controversial. Whether renal function status affects the ability of the TyG index to predict poor prognosis has not yet been elucidated and merits further studies.

METHODS: This retrospective cohort study included 22,031 participants from communities in the U.S. By juxtaposing the TyG categories with the estimated glomerular filtration rate (eGFR, either < 60 mL/min/1.73m² or ≥ 60 mL/min/1.73m²), participants were categorized into four distinct groups: (1) TyG_L/eGFR_H; (2) TyG_H/eGFR_H; (3) TyG_L/eGFR_L; and (4) TyG_H/eGFR_L. The endpoint was the all-cause mortality rate. Standard Kaplan-Meier plots were constructed and multifactor Cox regression analyses were carried out and restricted cubic spline regression analysis was utilized to assess the association between death and the TyG index for different renal function statuses.

RESULTS: No statistical differences were found in the TyG groups in participants with normal renal function after adjustment for all covariates (P = 0.070). However, in the high TyG index group with renal insufficiency, the risk of all-cause mortality rates was reduced by 18%. (HR, 0.82; CI, 0.69-0.98). The TyG index (high vs. low) and renal function (eGFR < 60 vs. eGFR ≥ 60) had statistically significant interactions with death (P < 0.001). When all covariates were adjusted, the risk of mortality for the TyG_L combined with eGFR_L group was 56% higher than that for the TyG_L combined with eGFR_H group (HR, 1.56; CI, 1.33-1.82). In the renal insufficiency population, a nonlinear relationship was observed between mortality and the TyG index, albeit with a differing pattern (P for nonlinearity < 0.001).

CONCLUSIONS: While it has been known that TyG index was a prognosis marker of CVD, this research highlights that higher TyG index was associated with higher all-cause mortality rates for all participants. Furthermore, renal function status significantly moderates the effect of the TyG index on all-cause mortality in community-dwelling adults.

PMID:37951945 | DOI:10.1186/s12944-023-01958-1

BMC Med Genomics. 2023 Nov 11;16(1):284. doi: 10.1186/s12920-023-01710-9.

ABSTRACT

Deep vein thrombosis (DVT) is the formation of a blood clot in a deep vein. DVT can lead to a venous thromboembolism (VTE), the combined term for DVT and pulmonary embolism, a leading cause of death and disability worldwide. Despite the prevalence and associated morbidity of DVT, the underlying causes are not well understood. Our aim was to leverage publicly available genetic summary association statistics to identify causal risk factors for DVT. We conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) using genetic summary association statistics for 973 exposures and DVT (6,767 cases and 330,392 controls in UK Biobank). There was evidence for a causal effect of 57 exposures on DVT risk, including previously reported risk factors (e.g. body mass index-BMI and height) and novel risk factors (e.g. hyperthyroidism and varicose veins). As the majority of identified risk factors were adiposity-related, we explored the molecular link with DVT by undertaking a two-sample MR mediation analysis of BMI-associated circulating proteins on DVT risk. Our results indicate that circulating neurogenic locus notch homolog protein 1 (NOTCH1), inhibin beta C chain (INHBC) and plasminogen activator inhibitor 1 (PAI-1) influence DVT risk, with PAI-1 mediating the BMI-DVT relationship. Using a phenome-wide approach, we provide putative causal evidence that hyperthyroidism, varicose veins and BMI enhance the risk of DVT. Furthermore, the circulating protein PAI-1 has a causal role in DVT aetiology and is involved in mediating the BMI-DVT relationship.

PMID:37951941 | DOI:10.1186/s12920-023-01710-9

Alzheimers Res Ther. 2023 Nov 11;15(1):198. doi: 10.1186/s13195-023-01341-3.

ABSTRACT

BACKGROUND: Subjective cognitive complaints (SCC) have been mostly studied in the context of Alzheimer’s disease in memory clinic settings. The potential of combining SCC with genetic information and blood biomarkers of neurodegenerative diseases for risk assessment of dementia and depression in the absence of dementia among community-dwelling older adults has so far not been explored.

METHODS: Data were based on a population-based cohort of 6357 participants with a 17-year follow-up (ESTHER study) and a clinic-based cohort of 422 patients. Participants of both cohorts were grouped according to the diagnosis of dementia (yes/no) and the diagnosis of depression in the absence of dementia (yes/no). Participants without dementia included both cognitively unimpaired participants and cognitively impaired participants. Genetic information (APOE ε4 genotype) and blood-based biomarkers of neurodegenerative diseases (glial fibrillary acidic protein; GFAP, neurofilament light chain; NfL, phosphorylated tau181; p-tau181) were available in the ESTHER study and were determined with Simoa Technology in a nested case-control design. Logistic regression models adjusted for relevant confounders were run for the outcomes of all-cause dementia and depression in the absence of dementia.

RESULTS: The results showed that persistent SCC were associated both with increased risk of all-cause dementia and of depression without dementia, independently of the diagnostic setting. However, the results for the ESTHER study also showed that the combination of subjective complaints with APOE ε4 and with increased GFAP concentrations in the blood yielded a substantially increased risk of all-cause dementia (OR 5.35; 95%CI 3.25-8.81, p-value < 0.0001 and OR 7.52; 95%CI 2.79-20.29, p-value < 0.0001, respectively) but not of depression. Associations of NfL and p-tau181 with risk of all-cause dementia and depression were not statistically significant, either alone or in combination with SCC, but increased concentrations of p-tau181 seemed to be associated with an increased risk for depression.

CONCLUSION: In community and clinical settings, SCC predict both dementia and depression in the absence of dementia. The addition of GFAP could differentiate between the risk of all-cause dementia and the risk of depression among individuals without dementia.

PMID:37951931 | DOI:10.1186/s13195-023-01341-3

BMC Health Serv Res. 2023 Nov 11;23(1):1240. doi: 10.1186/s12913-023-10302-3.

ABSTRACT

BACKGROUND: Many Nigerians pay out-of-pocket for their health care, and some hospitals have started utilising e-payment systems to increase transactional efficiency. The study investigated the type and usage of e-payment platforms in public hospitals and the factors that may influence the managerial staff’s disposition towards using the e-payment system.

METHODS: We conducted a cross-sectional survey of 300 managerial staff within the four public tertiary hospitals in Enugu, Nigeria, through proportionate quota sampling. The survey obtained participants’ demographic characteristics, types of e-payment platforms, managerial staff’s technophobia, perception of credibility, and disposition towards e-payment. Data were analysed using descriptive statistics, Spearman correlation, and hierarchical linear regression.

RESULTS: The majority of the respondents (n = 278, 92.7% completion rate) aged 43.4 ± 7.6 years were females (59.0%) with a bachelor’s degree (54.7%). Their disposition (80.0%±17.9%), perceptions of the usefulness (85.7 ± 13.9%), and user-friendliness (80.5 ± 18.1%) of e-payment in the hospital were positive, credibility (72.6 ± 20.1%) and technophobia (68.0 ± 20.7%) were moderate. There was a negative correlation between technophobia and disposition toward the use of e-payment (ρ = -0.50, P < 0.001). Significant multivariate predictors of managerial disposition towards e-payment were; being a woman (β = 0.12, P = 0.033), married (β = 0.18, P = 0.003), positive perception of usefulness (β = 0.14, P = 0.025), and credibility (β = 0.15, P = 0.032).

CONCLUSION: Most participants had a positive disposition towards e-payment in public hospitals. However, managers with technophobia, a negative perception of e-payment usefulness, and credibility had a lesser disposition to its use. To ensure the universal implementation of e-payment in Nigerian hospitals, the service providers should make the e-payment platforms more secure and user-friendly to health services consumers and providers.

PMID:37951924 | DOI:10.1186/s12913-023-10302-3